title: Induction of luciferase activity under the control of an hsp70 promoter using high-intensity focused ultrasound: combination of bioluminescence and MRI imaging in three different tumour models.
abstract: The in vivo temporal changes of luciferase activity were investigated under the control of an hsp70 promoter in three tumour models after the application of different intensities of high-intensity focused ultrasound (HIFU). Three cell lines, SCCVII, NIH3T3 and M21 were stably transfected with a plasmid containing the hsp70 promoter and luciferase reporter gene, and tumours were subcutaneously initiated into mice. At a size of 1300 ± 234 mm(3), the tumours were exposed to five intensities of continuous HIFU (802-1401-2157-3067-4133 W/cm(2)) for 20 sec. Bioluminescence and MR imaging were performed to assess luciferase activity and signal intensity changes in the tissue. The MRI scan protocol was pre- and post-contrast T1-wt-SE, T2-wt-FSE, DCE-MRI, diffusion-wt STEAM sequence, T2 relaxation time determination obtained on a 1.5-T GE MRI scanner. The NIH3T3 tumours showed the highest luciferase activity of 328.1 ± 7.1 fold at 24 h at a HIFU intensity of 3067 W/cm(2), the M21 tumours of 3.2 ± 0.6 fold 8 hours and the SCCVII tumours 2.9 ± 0.9 fold 4 hours post-HIFU at 2157 W/cm(2). The greatest increase in T2 signal intensity and T2 relaxation time of 20.7 ± 3.4% was seen in the SCCVII tumours. The highest contrast medium uptake of 10.1 ± 1.1% was noted in the M21 tumours, and 14.8 ± 1.9% in the SCCVII tumours. In all tumours, a significant increase in the diffusion coefficient was seen with increased HIFU intensity, the highest of which was 40.3 ± 4.1% in the SCCVII tumours. The three tumour cell lines stably transfected with the hsp70/luciferase gene showed differential luciferase activity, which peaked at different times after the application of HIFU and was dependant on tumour type and HIFU energy deposition.
authors.affiliation: Department of Radiology, Lucas MRS Research Center, Stanford School of Medicine, Stanford, CA 94305, USA. hundt@med.uni-marburg.de
authors.forename: W
authors.initials: W
authors.lastname: Hundt
authors.forename: S
authors.initials: S
authors.lastname: Steinbach
authors.forename: M
authors.initials: M
authors.lastname: Burbelko
authors.forename: A
authors.initials: A
authors.lastname: Kiessling
authors.forename: M
authors.initials: M
authors.lastname: Rominger
authors.forename: C E
authors.initials: CE
authors.lastname: O'Connell-Rodwell
authors.forename: D
authors.initials: D
authors.lastname: Mayer
authors.forename: M D
authors.initials: MD
authors.lastname: Bednarski
authors.forename: S
authors.initials: S
authors.lastname: Guccione
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014465:Ultrasonics
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; D008156:Luciferases